Yeast yapsins and cell wall assembly

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Our laboratory is interested in the regulation and functional role of a unique family of fungal enzymes, collectively known as 'yapsins', in the assembly of the yeast cell wall. This structure is highly complex and essential for the viability of all fungi, including human opportunist pathogens such as C. albicans. The first member of this family is the Yps1 enzyme that we, and others, identified in the brewer yeast S. cerevisiae a decade ago. We now know that five members of theses enzymes are expressed in S. cerevisiae, all of them are localized at the cell surface. Recent studies suggested that these enzymes were implicated in some aspects of cell wall assembly, but until recently, no substrate for any of these enzymes had been identified. We recently identified some natural substrates for Yps1 in S. cerevisiae and the nature of these substrates clearly confirmed that Yps1 participate in the cell wall assembly. Our recent study also suggested that: 1) during their intracellular transport to reach the cell surface, these enzymes are kept apart from most other proteins destined for secretion; and 2) the environmental pH regulates the activity of this enzyme. In the current proposal we have designed experiments to: 1) identify additional Yps1 substrates; 2) confirm and understand the significance of the particular intracellular transport that this enzyme is taking; and 3) understand what controls the activity of this enzyme. In addition to deepen our understanding on how fungal yapsins regulate cell wall assembly in yeast, the proposed studies should help designing specific inhibitors that may lead to the development of novel antifungal agents.